天然产物研究与开发 ›› 2023, Vol. 35 ›› Issue (6): 1049-1057.doi: 10.16333/j.1001-6880.2023.6.014

• 开发研究 • 上一篇    下一篇

响应面法优化paraherquamide A的发酵工艺

陈晓娜1,彭加飞2,王品美1,徐金钟1*   

  1. 1浙江大学海洋学院,舟山 316000;2极致生物技术(杭州)有限公司,杭州 311121
  • 出版日期:2023-06-28 发布日期:2023-06-28
  • 基金资助:
    舟山市校合作联合专项(2021C81004);海南省自然科学基金(321QN273)

Optimization of fermentation process of paraherquamide A by response surface methodology

CHEN Xiao-na1,PENG Jia-fei2,WANG Pin-mei1,XU Jin-zhong1*   

  1. 1Oceanography College,Zhejiang University,Zhoushan 316000,China;2Jizhi Biotechnology (Hangzhou) Co.,Ltd.,Hangzhou 311121,China
  • Online:2023-06-28 Published:2023-06-28

摘要:

Paraherquamide A(PA)作为新型驱虫药Startect®的重要原料,其产量制约药物的推广和使用。本研究采用响应面法系统对野生Penicillium sp.KWF31的PA发酵工艺进行优化。通过Plackett-Burman设计对培养基的8个因素进行筛选,得到显著影响效价的3个关键因素分别是酵母提取物、可溶性淀粉和葡萄糖。进而采用爬坡实验逼近这3个关键因素的最大响应区域,通过Box-Behnken设计建立数学模型,获得产PA的最佳条件为可溶性淀粉31.0 g/L、葡萄糖12.8 g/L、酵母提取物14.5 g/L。在此条件下,PA效价高达243.7 mg/L,与预测值241.6 mg/L相近,是优化前的3.4倍。

关键词: 响应面法, paraherquamide A, 驱虫药, 发酵, 海洋青霉

Abstract:

Paraherquamide A(PA) is an important raw material for the new anthelmintic drug Startect®,and its low yield limits the promotion and use of the drug.Response surface methodology (RSM) was used to optimize the fermentation process of wild Penicillium sp.KWF31 to produce PA.Eight factors of the medium were screened by Plackett-Burman test design.Among them,the dosages of soluble starch,glucose and yeast extract were found to be the key factors.The optimal concentration ranges of the three factors were examined by the steepest ascent path and the Box-Behnken design as 31.0 g/L soluble starch,12.8 g/L glucose and 14.5 g/L yeast extract,respectively.Under the optimal condition,the maximum titer of PA approached 243.7 mg/L,which was close to the theoretical value of 241.6 mg/L,and 3.4 times of the initial.

Key words: response surface methodology, paraherquamide A, anthelmintic, fermentation, marine Penicillium fungus

中图分类号:  R978.6 TQ463